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Mechanisms of tolerance to DNA damaging therapeutic drugs
Open accessAbstract
The cytotoxic effect of many anticancer drugs relies on their ability to damage DNA. Drug resistance can be associated with the ability to remove potentially lethal DNA lesions. DNA damage tolerance offers an alternative route to resistance. In a drug-tolerant cell, persistent DNA damage has become uncoupled from cell death. Tolerance to some DNA damaging drugs is accompanied by inactivation of the cell's DNA mismatch repair pathway. This is widely acknowledged as the mechanism underlying resistance to methylating agents and to 6-thioguanine which produce structurally similar types of DNA damage. Defects in mismatch repair are also associated with resistance to numerous drugs that produce a wide variety of structurally diverse DNA lesions. Here I consider possible mechanisms by which mismatch repair might influence drug resistance and the extent to which loss of mismatch repair might be considered to confer a multidrug resistance phenotype.
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Citations
Cited by
The multifaceted mismatch-repair system
Jiricny, J. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1907 · Cited by 1,370
Azathioprine and UVA Light Generate Mutagenic Oxidative DNA Damage
O'Donovan, P., Perrett, C. M., Zhang, X., Montaner, B., Xu, Y.-Z., Harwood, C. A., McGregor, J. M., Walker, S. L., Hanaoka, F., & Karran, P. (2005) · Science · doi:10.1126/science.1114233 · Cited by 631
Self-citationKarran, P., & Attard, N. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2292 · Cited by 477
Self-citationMismatch repair and DNA damage signalling
Stojic, L., Brun, R., & Jiricny, J. (2004) · DNA Repair · doi:10.1016/j.dnarep.2004.06.006 · Cited by 396
The role of PARP in DNA repair and its therapeutic exploitation
Javle, M., & Curtin, N. J. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.382 · Cited by 320
Metadata
- Authors
- Karran, P.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-12
- Volume
- 22
- Issue
- 12
- Pages
- 1931-1937
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2153980875
- Cited by
- 226
- References
- 0
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- bronze
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